Abstract

Background

Depression is characterised partly by blunted reactions to reward. However, tasks
probing this deficiency have not distinguished insensitivity to reward from insensitivity
to the prediction errors for reward that determine learning and are putatively reported
by the phasic activity of dopamine neurons. We attempted to disentangle these factors
with respect to anhedonia in the context of stress, Major Depressive Disorder (MDD),
Bipolar Disorder (BPD) and a dopaminergic challenge.

Methods

Six behavioural datasets involving 392 experimental sessions were subjected to a model-based,
Bayesian meta-analysis. Participants across all six studies performed a probabilistic
reward task that used an asymmetric reinforcement schedule to assess reward learning.
Healthy controls were tested under baseline conditions, stress or after receiving
the dopamine D2 agonist pramipexole. In addition, participants with current or past MDD or BPD were
evaluated. Reinforcement learning models isolated the contributions of variation in
reward sensitivity and learning rate.

Results

MDD and anhedonia reduced reward sensitivity more than they affected the learning
rate, while a low dose of the dopamine D2 agonist pramipexole showed the opposite pattern. Stress led to a pattern consistent
with a mixed effect on reward sensitivity and learning rate.

Conclusion

Reward-related learning reflected at least two partially separable contributions.
The first related to phasic prediction error signalling, and was preferentially modulated
by a low dose of the dopamine agonist pramipexole. The second related directly to
reward sensitivity, and was preferentially reduced in MDD and anhedonia. Stress altered
both components. Collectively, these findings highlight the contribution of model-based
reinforcement learning meta-analysis for dissecting anhedonic behavior.